Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNDLURR)

DOT Name	Sialic acid-binding Ig-like lectin 7 (SIGLEC7)
Synonyms	Siglec-7; Adhesion inhibitory receptor molecule 1; AIRM-1; CDw328; D-siglec; QA79 membrane protein; p75; CD antigen CD328
Gene Name	SIGLEC7
Related Disease	Cerebral infarction ( ) Glioma ( ) Non-insulin dependent diabetes ( ) Acute leukaemia ( ) Alzheimer disease ( ) Amyotrophic lateral sclerosis ( ) Atopic dermatitis ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Classic Hodgkin lymphoma ( ) Colon cancer ( ) Colon carcinoma ( ) Depression ( ) Epilepsy ( ) Hepatitis ( ) Huntington disease ( ) Leukemia ( ) Major depressive disorder ( ) Malignant glioma ( ) Matthew-Wood syndrome ( ) Neuroblastoma ( ) Non-alcoholic fatty liver disease ( ) Osteoarthritis ( ) Pancreatic ductal carcinoma ( ) Parkinson disease ( ) Retinoblastoma ( ) Rheumatoid arthritis ( ) Small lymphocytic lymphoma ( ) Squamous cell carcinoma ( ) T-cell leukaemia ( ) Triple negative breast cancer ( ) Type-1/2 diabetes ( ) Medulloblastoma ( ) Cognitive impairment ( ) Acute myelogenous leukaemia ( ) Ankylosing spondylitis ( ) Arthritis ( ) Esophageal squamous cell carcinoma ( ) Hyperglycemia ( ) Hyperinsulinemia ( ) Melanoma ( ) Myeloid leukaemia ( ) Nervous system disease ( ) Prostate cancer ( ) Prostate carcinoma ( )
UniProt ID	SIGL7_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1NKO; 1O7S; 1O7V; 2DF3; 2G5R; 2HRL
Pfam ID	PF13895 ; PF07686
Sequence	MLLLLLLPLLWGRERVEGQKSNRKDYSLTMQSSVTVQEGMCVHVRCSFSYPVDSQTDSDP VHGYWFRAGNDISWKAPVATNNPAWAVQEETRDRFHLLGDPQTKNCTLSIRDARMSDAGR YFFRMEKGNIKWNYKYDQLSVNVTALTHRPNILIPGTLESGCFQNLTCSVPWACEQGTPP MISWMGTSVSPLHPSTTRSSVLTLIPQPQHHGTSLTCQVTLPGAGVTTNRTIQLNVSYPP QNLTVTVFQGEGTASTALGNSSSLSVLEGQSLRLVCAVDSNPPARLSWTWRSLTLYPSQP SNPLVLELQVHLGDEGEFTCRAQNSLGSQHVSLNLSLQQEYTGKMRPVSGVLLGAVGGAG ATALVFLSFCVIFIVVRSCRKKSARPAADVGDIGMKDANTIRGSASQGNLTESWADDNPR HHGLAAHSSGEEREIQYAPLSFHKGEPQDLSGQEATNNEYSEIKIPK
Function	Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- and alpha-2,6-linked sialic acid. Also binds disialogangliosides (disialogalactosyl globoside, disialyl lactotetraosylceramide and disialyl GalNAc lactotetraoslylceramide). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Mediates inhibition of natural killer cells cytotoxicity. May play a role in hemopoiesis. Inhibits differentiation of CD34+ cell precursors towards myelomonocytic cell lineage and proliferation of leukemic myeloid cells (in vitro).
Tissue Specificity	Predominantly expressed by resting and activated natural killer cells and at lower levels by granulocytes and monocytes. High expression found in placenta, liver, lung, spleen, and peripheral blood leukocytes.
Reactome Pathway	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cerebral infarction	DISR1WNP	Definitive	Altered Expression	[1]
Glioma	DIS5RPEH	Definitive	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[3]
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[5]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[6]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[10]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[12]
Depression	DIS3XJ69	Strong	Genetic Variation	[13]
Epilepsy	DISBB28L	Strong	Altered Expression	[14]
Hepatitis	DISXXX35	Strong	Biomarker	[15]
Huntington disease	DISQPLA4	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Biomarker	[17]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[18]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[19]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[20]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[21]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[15]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[22]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[20]
Parkinson disease	DISQVHKL	Strong	Biomarker	[23]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[22]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[26]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[27]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[28]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[29]
Medulloblastoma	DISZD2ZL	moderate	Biomarker	[30]
Cognitive impairment	DISH2ERD	Disputed	Biomarker	[31]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[32]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[33]
Arthritis	DIST1YEL	Limited	Genetic Variation	[34]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Altered Expression	[35]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[36]
Hyperinsulinemia	DISIDWT6	Limited	Biomarker	[36]
Melanoma	DIS1RRCY	Limited	Biomarker	[37]
Myeloid leukaemia	DISMN944	Limited	Biomarker	[38]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[39]
Prostate cancer	DISF190Y	Limited	Altered Expression	[40]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[40]
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⏷ Show the Full List of 46 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sialic acid-binding Ig-like lectin 7 (SIGLEC7).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sialic acid-binding Ig-like lectin 7 (SIGLEC7).	[42]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sialic acid-binding Ig-like lectin 7 (SIGLEC7).	[43]
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References

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12	The ceramide moiety of disialoganglioside (GD3) is essential for GD3 recognition by the sialic acid-binding lectin SIGLEC7 on the cell surface.J Biol Chem. 2019 Jul 12;294(28):10833-10845. doi: 10.1074/jbc.RA118.007083. Epub 2019 May 28.
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15	Serum soluble sialic acid-binding immunoglobulin-like lectin-7 concentration as an indicator of liver macrophage activation and advanced fibrosis in patients with non-alcoholic fatty liver disease.Hepatol Res. 2020 Apr;50(4):466-477. doi: 10.1111/hepr.13464. Epub 2019 Dec 26.
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17	The membrane-proximal immunoreceptor tyrosine-based inhibitory motif is critical for the inhibitory signaling mediated by Siglecs-7 and -9, CD33-related Siglecs expressed on human monocytes and NK cells.J Immunol. 2004 Dec 1;173(11):6841-9. doi: 10.4049/jimmunol.173.11.6841.
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21	p75 neurotrophin receptor and fenretinide-induced signaling in neuroblastoma.Cancer Chemother Pharmacol. 2014 Feb;73(2):271-9. doi: 10.1007/s00280-013-2355-y. Epub 2013 Nov 20.
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23	Genetic Association Between NGFR, ADAM17 Gene Polymorphism, and Parkinson's Disease in the Chinese Han Population.Neurotox Res. 2019 Oct;36(3):463-471. doi: 10.1007/s12640-019-00031-z. Epub 2019 Apr 2.
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25	Phenotypic analysis of hairy cell leukemia: "variant" cases express the interleukin-2 receptor beta chain, but not the alpha chain (CD25).Blood. 1993 Jul 15;82(2):528-35.
26	p75 Nerve Growth Factor Receptor as a Specific Nerve Marker in the Diagnosis of Perineural Invasion of Squamous Cell Carcinoma.Am J Clin Pathol. 2019 May 3;151(6):574-583. doi: 10.1093/ajcp/aqz011.
27	Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox.Blood. 2002 Aug 15;100(4):1399-403. doi: 10.1182/blood-2002-01-0300.
28	Inhibition of Triple-Negative Breast Cancer Tumor Growth by Electroacupuncture with Encircled Needling and Its Mechanisms in a Mice Xenograft Model.Int J Med Sci. 2019 Nov 9;16(12):1642-1651. doi: 10.7150/ijms.38521. eCollection 2019.
29	Modulation of the p75 neurotrophin receptor using LM11A-31 prevents diabetes-induced retinal vascular permeability in mice via inhibition of inflammation and the RhoA kinase pathway. Diabetologia. 2019 Aug;62(8):1488-1500.
30	Neurotrophin receptors and heparanase: a functional axis in human medulloblastoma invasion.J Exp Clin Cancer Res. 2007 Mar;26(1):5-23.
31	A small molecule p75NTR ligand, LM11A-31, reverses cholinergic neurite dystrophy in Alzheimer's disease mouse models with mid- to late-stage disease progression.PLoS One. 2014 Aug 25;9(8):e102136. doi: 10.1371/journal.pone.0102136. eCollection 2014.
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33	Both baseline clinical factors and genetic polymorphisms influence the development of severe functional status in ankylosing spondylitis.PLoS One. 2012;7(9):e43428. doi: 10.1371/journal.pone.0043428. Epub 2012 Sep 12.
34	Soluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous arthritis in transgenic mice expressing transmembrane tumor necrosis factor alpha.Arthritis Rheum. 2006 Sep;54(9):2872-85. doi: 10.1002/art.22077.
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36	Mechanisms of TNF-alpha-induced insulin resistance.Exp Clin Endocrinol Diabetes. 1999;107(2):119-25. doi: 10.1055/s-0029-1212086.
37	Apoptosis related protein-1 triggers melanoma cell death via interaction with the juxtamembrane region of p75 neurotrophin receptor.J Cell Mol Med. 2012 Feb;16(2):349-61. doi: 10.1111/j.1582-4934.2011.01304.x.
38	Proteolytic processing of cut homeobox 1 by neutrophil elastase in the MV4;11 myeloid leukemia cell line.Mol Cancer Res. 2008 Apr;6(4):644-53. doi: 10.1158/1541-7786.MCR-07-0268.
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40	Tyrosine kinase inhibitor CEP-701 blocks the NTRK1/NGF receptor and limits the invasive capability of prostate cancer cells in vitro.Int J Oncol. 2007 Jan;30(1):193-200.
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